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  • Tailored therapeutic strategies for synovial sarcoma: receptor tyrosine kinase pathway analyses predict sensitivity to the mTOR inhibitor RAD001.

Tailored therapeutic strategies for synovial sarcoma: receptor tyrosine kinase pathway analyses predict sensitivity to the mTOR inhibitor RAD001.

Cancer letters (2014-02-05)
Hirohiko Yasui, Norifumi Naka, Yoshinori Imura, Hidetatsu Outani, Keiko Kaneko, Ken-Ichiro Hamada, Satoru Sasagawa, Nobuhito Araki, Takafumi Ueda, Kazuyuki Itoh, Akira Myoui, Hideki Yoshikawa
ABSTRACT

We examined efficacy of the mTOR inhibitor RAD001 to seek novel therapies for synovial sarcoma (SS). Although RAD001 had significant anti-tumor effects, its sensitivity differed among cell lines. Phospho-receptor tyrosine kinase (RTK) array analyses revealed c-MET phosphorylation in highly mTOR inhibitor-sensitive cells and PDGFRα (which induces intrinsic resistance to mTOR inhibitor) activation in less sensitive cells. Combined treatment with RAD001 and the PDGFR inhibitor pazopanib showed anti-tumor effects in xenograft models with less sensitive cells. Thus, evaluating activated RTKs in clinical samples may predict sensitivity to mTOR inhibitors, raising the possibility of a tailored therapy for SS.

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Supelco
Everolimus solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®